These studies will examine the hypothesis that somatostatin- and neurotensin-like peptides are of physiological significance in the regulation of gastric acid secretion and that the mechanism of their action is primarily of a paracrine rather than hormonal nature. A hormonal mode of action on acid secretion will be evaluated in conventional animal models by mimicking the plasma level of somatostatin and neurotensin-like immunoreactivity obtained following a physiological stimulus with exogenous peptide administration. Specific antagonists will be used to evaluate physiological significance and potential mechanisms of action. The re-evaluation of a hormonal mechanism is essential since previous studies are non-conclusive due to methodological limitations. A paracrine mode of action has previously not been functionally evaluated for any peptide and will be studied using a new microdialysis fiber method. The release, action and clearance of somatostatin and neurotensin will be investigated in the previously unexplored gastric tissue interstitial fluid compartment in situ, in vivo. New region specific radio-immunoassays will be developed and used in combination with chromatographic techniques to characterize and quantify different molecular variants. The amino acid sequences of somatostatin- and neurotensin-like peptides in rat gastrointestinal tissue will be determined since this species is commonly used in physiological studies. These studies will improve the understanding of the detection, release, action and catabolism of somatostatin- and neurotensin-like peptides and reveal if the mechanism of their action on acid secretion is of hormonal and/or paracrine nature.
